Periodontal disease is now recognized as the sixth clinical complication of diabetes mellitus. This association was based on clinical studies examining the prevalence of periodontitis in adults with diabetes. While a limited number of studies have examined the prevalence of periodontal disease in children and adolescents, and determined that increased gingival inflammation was present m young patients with diabetes, these studies suffer from a number of identifiable problems, including small sample size, heterogenous populations and a failure to consider patient variables related to diabetes (i.e., duration of disease, level of metabolic control). Studies in our laboratory have utilized a murine model to study the etiology of accelerated periodontal disease associated with diabetes and have implicated the increased expression and activation of the receptor for advanced glycation endproducts (RAGE) as a key step in generation of an exaggerated inflammatory response as measured by production of inflammatory cytokines and matrix metalloproteinases. Consequently, taking advantage of an established relationship with Naomi Berrie Diabetes Center on the Columbia Presbyterian Medical Center campus, we propose to broadly examine periodontal disease in children and adolescents with diabetes. We will determine the oral disease burden in children and adolescents with type 1 and type 2 diabetes, and examine the development of gingival inflammation/periodontal disease in the natural history of diabetes mellitus and in relation to other microvascular complications of disease, examine the pathologic mechanisms that account for development of periodontal pathology in young patients with type 1 and type 2 disease, and determine if periodontal therapy can improve metabolic management in adolescents with poor control. Lastly, we plan to develop an intervention for non-dental medical professionals to promote identification of oral disease and referral for treatment in children and adolescents with diabetes mellitus. These studies will markedly enhance our understanding of the pathologic basis and clinical course of the most recently described complication of a debilitating chronic disease.